Smita Sihag1, Tamar Nobel1, Meier Hsu2, Sergio De La Torre1, Kay See Tan2, Yelena Y Janjigian3, Geoffrey Y Ku3, Laura H Tang4, Abraham J Wu5, Steven B Maron3, Manjit S Bains1, David R Jones1, Daniela Molena1. 1. Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NW 10065. 2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. 3. Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY. 4. Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY. 5. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY.
Abstract
OBJECTIVE: To evaluate whether pCR exclusively defines major pathologic response to treatment with improved survival. SUMMARY BACKGROUND DATA: pCR after trimodality therapy for EAC is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. METHODS: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage TR in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. RESULTS: Among 788 patients, median follow-up was 37.5 months (range, 0.4-210.6); median OS was 48.3 months (95% CI, 42.2-58.8). Absence of residual nodal disease was independently associated with improved survival (P < 0.001). Survival curves for 90% to 99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90% to 99% and 100% TR was independently associated with improved OS, compared with 50% to 89% and <50% TR. CONCLUSIONS: ypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to ≥90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to ≥90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies.
OBJECTIVE: To evaluate whether pCR exclusively defines major pathologic response to treatment with improved survival. SUMMARY BACKGROUND DATA: pCR after trimodality therapy for EAC is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. METHODS: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage TR in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. RESULTS: Among 788 patients, median follow-up was 37.5 months (range, 0.4-210.6); median OS was 48.3 months (95% CI, 42.2-58.8). Absence of residual nodal disease was independently associated with improved survival (P < 0.001). Survival curves for 90% to 99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90% to 99% and 100% TR was independently associated with improved OS, compared with 50% to 89% and <50% TR. CONCLUSIONS: ypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to ≥90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to ≥90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies.
Authors: Karen Becker; Rupert Langer; Daniel Reim; Alexander Novotny; Christian Meyer zum Buschenfelde; Jutta Engel; Helmut Friess; Heinz Hofler Journal: Ann Surg Date: 2011-05 Impact factor: 12.969
Authors: Lucian R Chirieac; Stephen G Swisher; Jaffer A Ajani; Ritsuko R Komaki; Arlene M Correa; Jeffrey S Morris; Jack A Roth; Asif Rashid; Stanley R Hamilton; Tsung-Teh Wu Journal: Cancer Date: 2005-04-01 Impact factor: 6.860
Authors: Kenneth L Meredith; Jill M Weber; Kiran K Turaga; Erin M Siegel; Jim McLoughlin; Sarah Hoffe; Melis Marcovalerio; Nilay Shah; Scott Kelley; Richard Karl Journal: Ann Surg Oncol Date: 2010-02-06 Impact factor: 5.344
Authors: Bryan H Burmeister; B Mark Smithers; Val Gebski; Lara Fitzgerald; R John Simes; Peter Devitt; Stephen Ackland; David C Gotley; David Joseph; Jeremy Millar; John North; Euan T Walpole; James W Denham Journal: Lancet Oncol Date: 2005-09 Impact factor: 41.316
Authors: Manjit S Bains; Alexander Stojadinovic; Bruce Minsky; Valerie Rusch; Alan Turnbull; Robert Korst; Robert Ginsberg; David P Kelsen; David H Ilson Journal: J Thorac Cardiovasc Surg Date: 2002-08 Impact factor: 5.209
Authors: Joel Tepper; Mark J Krasna; Donna Niedzwiecki; Donna Hollis; Carolyn E Reed; Richard Goldberg; Krystyna Kiel; Christopher Willett; David Sugarbaker; Robert Mayer Journal: J Clin Oncol Date: 2008-03-01 Impact factor: 44.544
Authors: Bo Jan Noordman; Manon C W Spaander; Roelf Valkema; Bas P L Wijnhoven; Mark I van Berge Henegouwen; Joël Shapiro; Katharina Biermann; Ate van der Gaast; Richard van Hillegersberg; Maarten C C M Hulshof; Kausilia K Krishnadath; Sjoerd M Lagarde; Grard A P Nieuwenhuijzen; Liekele E Oostenbrug; Peter D Siersema; Erik J Schoon; Meindert N Sosef; Ewout W Steyerberg; J Jan B van Lanschot Journal: Lancet Oncol Date: 2018-06-01 Impact factor: 41.316
Authors: Antonio J Esgueva; Iris Noordhoek; Elma Meershoek-Klein Kranenbarg; Martin Espinosa-Bravo; Zoltán Mátrai; Andrii Zhygulin; Arvids Irmejs; Carlos Mavioso; Francesco Meani; Eduardo González; Murat Özdemir; Tanir Allweis; Karol Rogowski; Catarina Rodrigues Dos Santos; Henrique Mora; Riccardo Ponzone; Domenico Samorani; Cornelis van de Velde; Riccardo A Audisio; Isabel T Rubio Journal: Ann Surg Oncol Date: 2021-11-08 Impact factor: 5.344
Authors: Smita Sihag; Samuel C Nussenzweig; Henry S Walch; Meier Hsu; Kay See Tan; Sergio De La Torre; Yelena Y Janjigian; Steven B Maron; Geoffrey Y Ku; Laura H Tang; Pari M Shah; Abraham Wu; David R Jones; David B Solit; Nikolaus Schultz; Karuna Ganesh; Michael F Berger; Daniela Molena Journal: Clin Cancer Res Date: 2022-06-13 Impact factor: 13.801
Authors: Caitlin A Harrington; Rebecca A Carr; Meier Hsu; Kay See Tan; Smita Sihag; Prasad S Adusumilli; Manjit S Bains; Matthew J Bott; James M Isbell; Bernard J Park; Gaetano Rocco; Valerie W Rusch; David R Jones; Daniela Molena Journal: J Thorac Cardiovasc Surg Date: 2022-03-01 Impact factor: 6.439
Authors: Rebecca A Carr; Meier Hsu; Caitlin A Harrington; Kay See Tan; Manjit S Bains; Matthew J Bott; David H Ilson; James M Isbell; Yelena Y Janjigian; Steven B Maron; Bernard J Park; Valerie W Rusch; Smita Sihag; Abraham J Wu; David R Jones; Geoffrey Y Ku; Daniela Molena Journal: Ann Surg Date: 2021-08-13 Impact factor: 13.787